Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY(POS) mice

J Vet Med Sci. 2016 Jan;77(12):1587-98. doi: 10.1292/jvms.15-0292. Epub 2015 Jul 18.

Abstract

Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) in the "bipotential" gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XY(POS)) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XY(POS) mice, which were generated by backcrossing of B6J-XY(POS) on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XY(POS) mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XY(POS) gonads occurred 2-3 tail somites later than those in B6N-XY(B6) gonads, but earlier than those in B6J-XY(POS), respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XY(POS). Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XY(POS) testes and a male-related gene in the XY(POS) ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chromosomes, Mammalian / genetics
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Ovary / growth & development*
  • Ovotesticular Disorders of Sex Development / genetics*
  • Sex Determination Processes / genetics
  • Sex Determination Processes / physiology*
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / metabolism
  • Testis / growth & development*
  • X Chromosome / genetics*
  • Y Chromosome / genetics*

Substances

  • Sex-Determining Region Y Protein
  • Sry protein, mouse